This proposal seeks funds to continue a research program designed to increase our understanding of peptide conformation, inclusion complexes, ion-binding and ion transport through membranes on the molecular level. Peptides (hosts) capable of forming inclusion complexes with particles of biol gical significance (guests) will be synthesized. In particular, choline and amino acid binding peptides are proposed. In addition, membrane-active molecules (valinomycin-like ion-carriers) with ion-specificity (Na ion, K ion, Ca ions, Mg ions) will be prepared. As models for the study of some electrical phenomena (excitability) observed in heart muscle and nerve membranes, analogs of the pore-forming peptide alamethicin will be synthesized. New ways to probe and select accessible sites in resins for solid-phase peptide synthesis and to increase the yield of peptide cyclization are proposed. Porin, a membrane protein from E. coli will be modified to produce cation and anion-selective pores. The peptides will be syntheszed by a solid-phase fragment condensation scheme and purified by chromatography. Characterization will be by amino acid analyss, mass spectrometry, NMR spectroscopy and by measuring the guest/host ration. Experiments designed to determine guest-host binding constants will make use of the following methods: Two-phase extraction equilibria, NMR spectroscopy and electrical measurements with lipid bilayer membranes. The latter method will also be used to determine the transport mechanism of the ion-carriers and to assay synthetic alamethicin analogs.